SHOX2 promotes prostate cancer proliferation and metastasis through disruption of the Hippo-YAP pathway
Wenjie Yang,
Hualin Chen,
Lin Ma,
Jie Dong,
Mengchao Wei,
Xiaoqiang Xue,
Yingjie Li,
Zhaoheng Jin,
Weifeng Xu,
Zhigang Ji
Affiliations
Wenjie Yang
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100000, China
Hualin Chen
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100000, China
Lin Ma
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100000, China
Jie Dong
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100000, China
Mengchao Wei
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100000, China
Xiaoqiang Xue
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100000, China
Yingjie Li
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100000, China
Zhaoheng Jin
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100000, China
Weifeng Xu
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100000, China; Corresponding author
Zhigang Ji
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100000, China; Corresponding author
Summary: The transcription factor SHOX2 gene is critical in regulating gene expression and the development of tumors, but its biological role in prostate cancer (PCa) remains unclear. In this study, we found that SHOX2 expression was significantly raised in PCa tissues and was associated with clinicopathological features as well as disease-free survival (DFS) of PCa patients. Phenotypic tests showed that the absence of SHOX2 inhibited PCa growth and invasion, while SHOX2 overexpression promoted these effects. Mechanistically, SHOX2 was found to activate the transcription of nephronophthisis type 4 (NPHP4), a gene located downstream of SHOX2. Further analysis revealed that SHOX2 could potentially interfere with the Hippo-YAP signaling pathway through NPHP4 activation, facilitating the oncogenic behavior of PCa cells. These findings highlight SHOX2 as an oncogene in PCa and provide a basis for developing potential therapeutic approaches against this disease.
